In depth studies were made to assess 1) the immunogenicity of H-2 and Ia antigen found in mouse serum, 2) the structural relationship between H-2 and tumor associated antigens and 3) the nature of possible H-2-viral interactions. Relatively small amounts of xenoantibody to serum H-2k and Iak were produced in rabbits as determined by Fab2 blocking of alloantisera, lysostrip techniques and by the inhibition of alloantiserum absorption by the absorption-inhibition method. Immunodepletion experiments, coupled with SDS-PAGE analyses and complement-dependent cytotoxicity assays clearly indicated that H-2.23 and tumor associated antigens were part of the same antigenic complex 6C3HED murine lymphosarcoma cells. Ascites fluid from tumor bearing mice were found 10-20 times the amount of H02 antigens found in serum or CFA-induced ascites fluid of normal mice. Rosette formation with sheep erythrocytes correlated well with the percentage of normal and tumor cells in a given preparation with only tumor cells being reactive. Specific immunodepletion together with immunoadsorbent experiments and SDS-PAGE analyses showed that H-2 antigens on vesicular stomatitis virus infected cells are associated with virally determined antigenic specificities.